WO 02/30405 (NeuroSearch A/S) describes a group of 8-azabicyclo[3.2.1]oct-2-ene derivatives having the dual activity of a nicotinic reuptake inhibitor and a monoamine agonist or antagonist or a monoamine reuptake inhibitor. One of the compounds disclosed is the racemate (±)-3-(2-benzothienyl)-8H-8-azabicyclo[3.2.1]-oct-2-ene (compound 1D1, method D, page 16).
We have now discovered that rather than having a dual activity, the enantiomers of 8-azabicyclo[3.2.1]oct-2-ene derivatives, such as (±)-3-(2-benzothienyl)-8H-8-azabicyclo[3.2.1]oct-2-ene, show an interesting pharmacological profile as monoamine reuptake inhibitors, in particular as regards the level of activity on reuptake of the monoamine neurotransmitters serotonin, dopamine and noradrenaline, such as the ratio of the serotonin reuptake versus the noradrenaline and dopamine reuptake activity.
Further it is often desirable, and sometimes subject to regulatory demands, to undertake drug development on specific enantiomers rather than racemic drugs. This rationale is based on the findings that often the desired characteristics of chiral compounds reside with one of its enantiomers, while the other enantiomer might in fact add to a potential toxicological effect of the drug.
Also, in order to allow thorough investigation of each enantiomer, enantiopure compounds and processes for obtaining enantiopure such compounds of chiral compounds are of significant importance for drug development.